Fahad I. Al-Jenoobi

Solid dispersions: a strategy for poorly aqueous soluble drugs and technology updates

Introduction: Present article reviews solid dispersion (SD) technologies and other patented inventions in the area of pharmaceutical SDs, which provide stable amorphous SDs. Areas covered: The review briefly compiles different techniques for preparing SDs, their applications, characterization of SDs, types of SDs and also elaborates the carriers used to prepare SDs. The advantages of recently introduced SD technologies such as RightSize™, closed-cycle spray drying (CSD), Lidose® are summarized. Stability-related issues like phase separation, re-crystallization and methods to curb these problems are also discussed. A patented carrier-screening tool for predicting physical stability of SDs on the basis of drug–carrier interaction is explained. Applications of SD technique in controlled drug delivery systems and cosmetics are explored. Review also summarizes the carriers such as Soluplus®, Neusilin®, SolumerTM used to prepare stable amorphous SD. Expert opinion: Binary and ternary SDs are found to be more stable and provide better enhancement of solubility or dissolution of poorly water-soluble drugs. The use of surfactants in the carrier system of SD is a recent trend. Surfactants and polymers provide stability against re-crystallization of SDs, surfactants also improve solubility and dissolution of drug.

Everted gut sac model as a tool in pharmaceutical research: limitations and applications.

Objectives  This review discusses the limitations and applications of the everted gut sac model in studying drug absorption, metabolism, and interaction.

Enhanced anti-inflammatory activity of carbopol loaded meloxicam nanoethosomes gel

The aim of the current investigation is to develop nanoethosomes for transdermal meloxicam delivery. The ethosomes were prepared by varying the variables such as concentrations of phospholipids 90G, ethanol, and sonication time while entrapment efficiency, vesicle size and transdermal flux were the chosen responses. Results indicate that the nanoethosomes of meloxicam provides lesser vesicles size, better entrapment efficiency and improved flux for transdermal delivery as compared to rigid liposomes. The optimized formulation (MCEF-OPT) obtained was further evaluated for an in vivo anti-inflammatory activity in rats. Optimized nanoethosomal formulation with vesicles size of 142.3nm showed 78.25% entrapment efficiency and achieved transdermal flux of 10.42μg/cm(2)/h. Nanoethosomes proved to be significantly superior in terms of, amount of drug permeated into the skin, with an enhancement ratio of 3.77 when compared to rigid liposomes. In vivo pharmacodynamic study of carbopol(®) loaded nanoethosomal gel showed significant higher percent inhibition of rat paw edema compared with oral administration of meloxicam. Our results suggest that nanoethosomes are an efficient carrier for transdermal delivery of meloxicam.

Commercially bioavailable proprietary technologies and their marketed products

In this review, we discuss the methodologies and platform technologies for enhancing the oral bioavailability of poorly soluble drugs. We also highlight the mechanisms of formulation technologies for improving desired physicochemical attributes of active substances. We focus on various commercial technologies, along with marketed products, and identify proprietary technologies protected by patents. We also discuss nonpropriety technologies, such as mesoporous silica, cyclodextrin complexation and solid dispersions. In addition, we highlight the factors affecting drug absorption and/or bioavailability, the methodologies available to prepare bioavailability-enhanced products, stability issues and examples of technology implementation.

Environmentally Responsive Ophthalmic Gel Formulation of Carteolol Hydrochloride

Environmentally responsive gel formulation for ocular controlled delivery of carteolol hydrochloride (HCl) was developed in an attempt to improve ocular bioavailability and hence decrease its systemic absorption and side effects. The viscosity and the ability of the prepared formulations to deliver carteolol HCl in vitro and in vivo were monitored and compared with an aqueous commercial solution. The effect of polymer concentration and drug concentration on the in vitro release of carteolol HCl was examined. Gelrite formulations showed pseudoplastic behavior with thixotropic characteristics and the viscosity of the prepared systems increased as the concentration of the polymer increased. At fixed drug concentrations, as the Gelrite concentration increased, the drug release decreased. At fixed polymer concentrations, as the drug concentration increased the release of drug increased. Gelrite formulation (0.4% w/w) containing 1% drug showed significantly improved bioavailability compared with the commercial aqueous solution (Arteoptic® 1%). The developed in situ gel formulation showed potential for use as delivery systems with superior ocular bioavailability of carteolol HCl.

Transdermal delivery of calcium channel blockers for hypertension

Introduction: Calcium channel blockers are a very important class of antihypertensive drugs. Most calcium channel blockers (CCBs) exhibiting low oral bioavailability are required to be taken more than once a day due to their short half-lives which result in poor patient compliance. There is an ineluctable requirement for improved drug-delivery devices for CCBs because of the quantum of their utilization and shortcoming associated with their conventional dosage forms. Areas covered: There have been worthwhile research endeavors worldwide to investigate the skin permeation and to develop transdermal formulations of various categories of CCBs. This review explores the investigations on the feasibility and applicability of systemic delivery of various CCBs via skin. Expert opinion: Transdermal delivery of CCBs has been particularly acknowledged as a potential drug-delivery route in the therapy of hypertension. Several overtures have been made to enhance delivery of these drugs via skin barrier. There have been remarkable research endeavors worldwide to investigate the skin permeation and to develop transdermal systems of various CCBs. Persistent advancement in this area holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.

Transdermal delivery of angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) and others for management of hypertension

Abstract Context: Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) are some of the most commonly prescribed medications for hypertension. Objective: Most of all conventional dosage forms of ARBs and ACEIs undergo extensive first-pass metabolism, which significantly reduces bioavailability. Majority of ARBs and ACEIs are inherently short acting due to a rapid elimination half-life. In addition, oral dosage forms of ARBs and ACEIs have many high incidences of adverse effects due to variable absorption profiles, higher frequency of administration and poor patient compliance. Methods: Many attempts have been made globally at the laboratory level to investigate the skin permeation and to develop transdermal therapeutic systems of various ARBs, ACEIs and other anti-hypertensives, to circumvent the drawbacks associated with their conventional dosage form. Results: This manuscript presents an outline of the transdermal research specifically in the area of ARBs, ACEIs and other anti-hypertensives reported in various pharmaceutical journals. Conclusion: The transdermal delivery has gained a significant importance for systemic treatment as it is able to avoid first-pass metabolism and major fluctuations of plasma levels typical of repeated oral administration. As we can experience from this review article that transdermal delivery of different ARBs and ACEIs improves bioavailability as well as patient compliance by many folds. In fact, the rationale development of some newer ARBs, ACEIs and other anti-hypertensives transdermal systems will provide new ways of treatment, circumventing current limitations for conventional dosage forms.

Effect of Black Seed on Dextromethorphan O- and N-Demethylation in Human Liver Microsomes and Healthy Human Subjects

OBJECTIVE To investigate the effects of black seed on the metabolic activities of CYP3A4 and CYP2D6 in human liver microsomes and in human subjects using dextromethorphan as a probe drug. METHODS CYP2D6-mediated O-demethylation and CYP3A4-mediated N-demethylation of dextromethorphan (DEX) to dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively, were utilized to assess the metabolic activities of the two enzymatic pathways. In the in vitro experiments, DEX was incubated with microsomes and NADPH in absence or presence of black seed extract (10-100 microg/ml) and the formation of the metabolites were measured by HPLC. In the clinical study, four healthy volunteers received a single oral dose of DEX 30 mg alone in phase I, and along with last dose of black seed (2.5 g twice daily for seven days) in phase II. Activities of the two enzymes were evaluated based on the urinary metabolic ratios (MRs), which were calculated from eight-hour urine collections. DEX and its metabolites were assayed in urine samples by HPLC following a liquid-liquid extraction. RESULTS Black seed extracts significantly inhibited the formation of both metabolites in microsomes. The maximum inhibition was observed at the highest extract concentration (i.e., 100 microg/ml), which was about 80% and 60% for DOR and 3-MM, respectively. In the clinical study, the urinary MRs of DEX/DOR and DEX/3-MM increased by factors of 127 and 1.6-fold, respectively, after consumption of black seed. CONCLUSION Black seed significantly inhibited CYP2D6 and CYP3A4 mediated metabolism of DEX in human liver microsomes and healthy human volunteers indicating that it has the potential to interact with CYP2D6 and CYP3A4 substrates.

Systemic delivery of β-blockers via transdermal route for hypertension

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.

Effects of Nigella sativa and Lepidium sativum on Cyclosporine Pharmacokinetics

The present study was conducted to investigate the effects of Nigella sativa and Lepidium sativum on the pharmacokinetics of cyclosporine in rabbits. Two groups of animals were treated separately with Nigella sativa (200 mg/kg p.o.) or Lepidium sativum (150 mg/kg p.o.) for eight consecutive days. On the 8th day, cyclosporine (30 mg/kg p.o.) was administered to each group one hour after herbal treatment. Blood samples were withdrawn at different time intervals (0.0, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, and 24 hrs) from marginal ear vein. Cyclosporine was analyzed using UPLC/MS method. The coadministration of Nigella sativa significantly decreased the C max and AUC0−∞ of cyclosporine; the change was observed by 35.5% and 55.9%, respectively (P ≤ 0.05). Lepidium sativum did not produce any significant change in C max of cyclosporine, although its absorption was significantly delayed compared with control group. A remarkable change was observed in T max and AUC0−t of Lepidium sativum treated group. Our findings suggest that concurrent consumption of Nigella sativa and Lepidium sativum could alter the pharmacokinetics of cyclosporine at various levels.